Identification of a novel nonsense mutation in α-galactosidase A that causes Fabry disease in a Chinese family.

Fabry disease, a lysosomal storage disease, is an uncommon X-linked recessive genetic disorder stemming from abnormalities in the alpha-galactosidase gene (GLA) that codes human alpha-Galactosidase A (α-Gal A). To date, over 800 GLA mutations have been found to cause Fabry disease (FD). Continued enhancement of the GLA mutation spectrum will contribute to a deeper recognition and underlying mechanisms of FD. In this study, a 27-year-old male proband exhibited a typical phenotype of Fabry disease. Subsequently, family screening for Fabry disease was conducted, and high-throughput sequencing was employed to identify the mutated gene. The three-level structure of the mutated protein was analyzed, and its subcellular localization and enzymatic activity were determined. Apoptosis was assessed in GLA mutant cell lines to confirm the functional effects. As a result, a new mutation, c.777_778del (p. Gly261Leufs*3), in the GLA gene was identified. The mutation caused a frameshift during translation and the premature appearance of a termination codon, which led to a partial deletion of the domain in C-terminal region and altered the protein's tertiary structure. In vitro experiments revealed a significant reduction of the enzymatic activity in mutant cells. The expression was noticeably decreased at the mRNA and protein levels in mutant cell lines. Additionally, the subcellular localization of α-Gal A changed from a homogeneous distribution to punctate aggregation in the cytoplasm. GLA mutant cells exhibited significantly higher levels of apoptosis compared to wild-type cells.

FOXP3 gene polymorphisms increase the risk of systemic lupus erythematosus in a Han Chinese population.

BACKGROUND: FOXP3 is a transcription factor that regulates the development and function of Treg, playing an essential role in preventing autoimmune diseases. Variation in FOXP3 can impair the function of Treg cells, thus destroying their inhibitory capacity and leading to autoimmune diseases. This paper investigated whether the three SNPs in the FOXP3 gene (-3279 C/A, -924 A/G and -6054 del/ATT) are associated with systemic lupus erythematosus (SLE) susceptibility in the Han Chinese population. MATERIALS AND METHODS: The study cohort comprised 122 SLE patients and 268 healthy controls. Genotyping was performed by polymerase chain reaction sequence-specific primer (PCR-SSP). Furthermore, we examined the potential clinical manifestations associated with FOXP3 polymorphisms in SLE patients. RESULTS: The results showed that the -3279 (C > A) was significantly associated with the SLE risk in a homozygote (OR = 3.24, 95% CI = 1.23-8.52, p = .013, AA vs. CC), dominant (OR = 1.68, 95% CI = 1.07-2.65, p = .025, AC + AA vs. CC), recessive (OR = 2.90, 95% CI = 1.12-7.55, p = .023, AA vs. AC + CC) and allelic (OR = 1.72, 95% CI = 1.18-2.53, p = .005, A vs. C) models. In addition, -924 (A > G) was positively associated with SLE risk in the heterozygote (OR = 1.66, 95% CI = 1.04-2.66, p = .033, AG vs. AA) and dominant (OR = 1.59, 95% CI = 1.01-2.49, p = .042, AG + GG vs. AA) models, whereas -6054 (del > ATT) was not associated with SLE. Moreover, the immunological index analysis suggested that decreased complement C4 occurred more frequently in SLE patients carrying the minor allele (A) -3279 (C > A) than those not (p = .005). CONCLUSIONS: We demonstrated that -3279 (C > A) and -924 (A > G) were associated with an increased risk of SLE and the immunological index, indicating that the FOXP3 variation is potentially related to the occurrence and development of SLE.

Genetic polymorphisms linked to extreme postorthodontic external apical root resorption in Koreans.

BACKGROUND: External apical root resorption (EARR) is a common undesirable outcome of orthodontic treatment, this study aimed to identify genetic polymorphisms associated with the susceptibility to extreme orthodontic-induced EARR in a Korean population using extreme phenotype analysis sampling. METHODS: Genomic DNA was isolated from the saliva of 77 patients who underwent orthodontic treatment involving two maxillary premolar extractions. The patients were divided into two groups based on EARR values measured on periapical radiographs: The significant resorption group (SG, EARR ≥ 4 mm) and the normal group (NG, EARR < 2 mm). In the NG group, patients with EARR < 1 mm were named the non-resorption group (NonG). Targeted next-generation sequencing was performed using the screened single nucleotide polymorphisms (SNPs), and firth logistic regression analysis was used to determine genetic associations with EARR. Haplotype-based association analysis was performed for specific SNPs. RESULTS: SNPs related to genes TNFSF11, TNFRSF11B, WNT3A, SFRP2, LRP6, P2RX7, and LRP1 were found to be significantly associated with severe EARR (p < 0.05, pre-Bonferroni correction p-values). Additionally, the haplotype CCA of rs17525809, rs208294, and rs1718119 P2RX7 had a higher frequency in the SG group. CONCLUSION: Extreme phenotype analysis has identified eleven SNPs related to genes TNFSF11, TNFRSF11B, WNT3A, SFRP2, LRP6, P2RX7, and LRP1 that are associated with severe root resorption in the Korean population. These findings will contribute to the development of predictive diagnostic tools for identifying severe root resorption that may occur during orthodontic treatment.

Causal relationship between blood traits and severe influenza A(H1N1)pdm09 infection in East Asian: A Mendelian randomization study.

Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two-sample Mendelian randomization analysis. Based on the data from our in-house genome-wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303-143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, ß = -3.212, p = 0.019), low-density-lipoprotein cholesterol (LDL-C, ß = -1.372, p = 0.045), and basophil counts (Baso, ß = -1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL-C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza.

Detection of α-thalassemia South-East Asian deletion based on a fully integrated digital polymerase chain reaction system DropXpert S6.

OBJECTIVES: This study aimed to establish a droplet digital polymerase chain reaction (ddPCR) assay for South-East Asian (SEA) deletion based on a fully integrated digital PCR system DropXpert S6. METHODS: A total of 151 whole blood samples, 10 chorionic villus samples, and 17 amniotic fluid samples were collected, including 106 SEA heterozygotes, 43 normal individuals, 10 Hb Bart's hydrops details, and 19 SEA deletions combined with other genotypes.Genotypes of these samples were determined by the Gap-PCR method. We perform a series of optimizations of the ddPCR system to ensure the performance of the entire ddPCR reaction, such as droplet stability, fluorescence clustering, sensitivity, and accuracy. RESULTS: Our assay exhibited 99.4% (177/178) accuracy compared with the Gap-PCR method, and the minimum detection limit of DNA was 0.1 ng/µL.Both targets have reliable linearity, R2 = 0.9999 for the α-thalassemia SEA deletion allele and R2 = 1 for the wild-type allele. The coefficient of variation for α-thalassemia SEA deletion allele detection at 2 and 10 ng/µL concentrations was 5.42% and 1.91%, respectively. In contrast, the coefficient of variation for wild-type allele detection was 4.06% and 1.83%, demonstrating its high quantitative accuracy. In addition, the DropXpert S6 PCR system showed some advantages over other ddPCR instruments, such as reducing testing costs, simplifying and automating the workflow. CONCLUSIONS: The DropXpert S6 PCR system provided a highly accurate diagnosis for α-thalassemia SEA deletion and can be used to detect α-thalassemia as an alternative method.

The novel KIR2DL3*037 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

The novel KIR2DL3*037 allele differs from the closest allele KIR2DL3*00101 by a single missense mutation.

Recognition of the HLA-DQB1*03:96 allele in a Taiwanese individual.

One nucleotide substitution in codon 130 of HLA-DQB1*03:03:02:01 results in a novel allele HLA-DQB1*03:96.

The characteristics and prevalence of patent foramen ovale in Japanese people: a study using material from forensic autopsies.

Racial and ethnic differences in the prevalence of patent foramen ovale have been suggested, but there are insufficient data to confirm the situation. Studies have also not investigated detailed morphological changes in the fossa ovalis by age. This study therefore aimed to clarify the characteristics of the fossa ovalis and determine the frequency of patent foramen ovale in Japanese people, using materials from forensic autopsies. A total of 359 hearts were obtained during forensic autopsies (from 223 males and 136 females, aged from 0 to 94 years). Overall, prevalence of patent foramen ovale was 12.5%, but it was significantly higher among those under 20 years old (66.7% in males, 38.5% in females). The area of the fossa ovalis linearly increased with age in both sexes. The prevalence of patent foramen ovale was lower in Japanese adults than previously found in either White or Black people. The ratio of the area of the fossa ovalis to the heart weight was nearly constant.

[Development and evaluation of the simplified Chinese versions of motion sickness susceptibility questionnaire].

Objective: To develop and evaluate the simplified Chinese versions of motion sickness susceptibility questionnaire (MSSQ)-long (MSSQ-L) and MSSQ-short (MSSQ-S). Methods: A cross-sectional study was conducted in May 2023 among 3 426 university students at North China University of Science and Technology. The Chinese versions of MSSQ-L and MSSQ-S were distributed, and item selection for Simplified Chinese versions of MSSQ-L and MSSQ-S was performed based on item response rates, item-total correlations, Cronbach's alpha coefficients, and standard deviations. Forty-five male and forty-five female participants were recruited from the initial survey population to complete Coriolis acceleration endurance testing and fill out the simplified Chinese versions of MSSQ-L and MSSQ-S, and Graybiel symptom severity score questionnaire. Internal consistency, external consistency, criterion validity, discriminant validity, and predictive accuracy for motion sickness severity were assessed. Results: A total of 3 111 valid responses were received for the Chinese versions of MSSQ, yielding an effective response rate of 90.8% (3 111/3 426). Among the 3 111 students surveyed, there were 965 males and 2 146 females, with a mean age of (19.5±1.4) years. The highest usage rates for item were observed for cars (98.9%, 3 077/3 111) and buses (98.8%, 3 073/3 111). The simplified Chinese versions of MSSQ-L and MSSQ-S consisted of four and eight items, respectively. The Cronbach's alpha coefficients were 0.900 and 0.953 for the simplified Chinese versions of MSSQ-S and MSSQ-L, respectively, with test-retest reliabilities of 0.895 and 0.908. Criterion validity coefficients were 0.814 and 0.765 for the simplified Chinese versions of MSSQ-S and MSSQ-L, respectively. In terms of discriminant validity, significant differences were observed between mild and moderate susceptibility groups [0(0, 3) vs 6(2, 10), P=0.006] and between moderate and severe susceptibility groups [6(2, 10) vs 9(6, 13), P=0.030] for the simplified Chinese version of MSSQ-S. Significant differences were also observed between mild and moderate susceptibility groups [5(0, 3) vs 7(3, 10), P=0.001], but not between moderate and severe susceptibility groups [7(3, 10) vs 7(3, 10), P=0.081] for simplified Chinese version of MSSQ-L. The overall predictive accuracy for motion sickness severity improved from 55.6% (50/90) to 62.2% (56/90) for the simplified Chinese version of MSSQ-S and from 54.4% (49/90) to 58.9% (53/90) for the simplified Chinese version of MSSQ-L, but with no statistically significant differences (both P>0.05). Conclusions: The simplified Chinese versions of MSSQ-L and MSSQ-S demonstrates good reliability and validity. The simplified Chinese version of MSSQ-S exhibits satisfactory discriminant validity, and can serve as a simple and efficient tool for assessing motion sickness susceptibility.

Association of TLR4 gene rs4986790 and rs4986791 polymorphisms with asthma susceptibility: meta-analysis and trial sequential analysis.

BACKGROUND: The current understanding of the correlation between TLR4 gene (toll-like receptor 4) rs4986790 and rs4986791 polymorphisms and asthma susceptibility is inconclusive, with studies and populations yielding conflicting results. OBJECTIVES: Evaluate this relationship using meta-analysis and trial sequential analysis (TSA). PATIENTS AND METHODS: Databases were systematically queried for relevant articles from the establishment of the database to 19 June 2023 adhering to predefined inclusion and exclusion criteria. Two authors independently conducted screening, data extraction, and quality evaluation. Meta-analysis and TSA were carried out using RevMan 5.4, StataMP 17.0, and TSA 0.9.5.10 Beta, with α=0.05. Subgroup analyses were conducted based on racial demographics. A sensitivity analysis was conducted employing a one-by-one exclusion method. Publication bias was assessed using the Begg and Egger tests. MAIN OUTCOME MEASURES: Association of asthma susceptibility with TLR4 gene rs4986790 and rs4986791 polymorphisms. SAMPLE SIZE: 23 articles included 22 studies on the rs4986790 polymorphism and 11 studies on the rs4986791 polymorphism on the TLR4 gene. RESULTS: Out of 692 studies screened, 23 met the inclusion criteria. While the overall meta-analysis showed no significant association between the TLR4 rs4986790 polymorphism and asthma susceptibility, subgroup analysis revealed a significant link in the Caucasian population. A significant association was noted in the meta-analysis, particularly among Asian populations, on the rs4986791 polymorphism. The sensitivity analysis indicated that the meta-analysis results were relatively stable. Publication bias analysis revealed minimal influence from publication bias. However, TSA was underscored by the necessity for additional original studies to further validate specific outcomes. CONCLUSIONS: Our study underscores the ethnicity-specific impact on the relationship between TLR4 polymorphisms and asthma susceptibility. While the overall findings for rs4986790 were not significant, the association with the Caucasian population merits further investigation. Furthermore, rs4986791 demonstrated a significant correlation with asthma susceptibility, specifically among Asian populations. LIMITATIONS: Our study predominantly examined the rs4986790 and rs4986791 polymorphisms, overlooking the potential influence of other genetic variants within TLR4.

Age Estimation by Machine Learning and CT-Multiplanar Reformation of Cranial Sutures in Northern Chinese Han Adults.

OBJECTIVES: To establish age estimation models of northern Chinese Han adults using cranial suture images obtained by CT and multiplanar reformation (MPR), and to explore the applicability of cranial suture closure rule in age estimation of northern Chinese Han population. METHODS: The head CT samples of 132 northern Chinese Han adults aged 29-80 years were retrospectively collected. Volume reconstruction (VR) and MPR were performed on the skull, and 160 cranial suture tomography images were generated for each sample. Then the MPR images of cranial sutures were scored according to the closure grading criteria, and the mean closure grades of sagittal suture, coronal sutures (both left and right) and lambdoid sutures (both left and right) were calculated respectively. Finally taking the above grades as independent variables, the linear regression model and four machine learning models for age estimation (gradient boosting regression, support vector regression, decision tree regression and Bayesian ridge regression) were established for northern Chinese Han adults age estimation. The accuracy of each model was evaluated. RESULTS: Each cranial suture closure grade was positively correlated with age and the correlation of sagittal suture was the highest. All four machine learning models had higher age estimation accuracy than linear regression model. The support vector regression model had the highest accuracy among the machine learning models with a mean absolute error of 9.542 years. CONCLUSIONS: The combination of skull CT-MPR and machine learning model can be used for age estimation in northern Chinese Han adults, but it is still necessary to combine with other adult age estimation indicators in forensic practice.

Dental Age Estimation in Northern Chinese Han Children and Adolescents Using Demirjian's Method Combined with Machine Learning Algorithms.

OBJECTIVES: To investigate the application value of combining the Demirjian's method with machine learning algorithms for dental age estimation in northern Chinese Han children and adolescents. METHODS: Oral panoramic images of 10 256 Han individuals aged 5 to 24 years in northern China were collected. The development of eight permanent teeth in the left mandibular was classified into different stages using the Demirjian's method. Various machine learning algorithms, including support vector regression (SVR), gradient boosting regression (GBR), linear regression (LR), random forest regression (RFR), and decision tree regression (DTR) were employed. Age estimation models were constructed based on total, female, and male samples respectively using these algorithms. The fitting performance of different machine learning algorithms in these three groups was evaluated. RESULTS: SVR demonstrated superior estimation efficiency among all machine learning models in both total and female samples, while GBR showed the best performance in male samples. The mean absolute error (MAE) of the optimal age estimation model was 1.246 3, 1.281 8 and 1.153 8 years in the total, female and male samples, respectively. The optimal age estimation model exhibited varying levels of accuracy across different age ranges, which provided relatively accurate age estimations in individuals under 18 years old. CONCLUSIONS: The machine learning model developed in this study exhibits good age estimation efficiency in northern Chinese Han children and adolescents. However, its performance is not ideal when applied to adult population. To improve the accuracy in age estimation, the other variables can be considered.

Comprehensive transcriptome profiling between balding and non-balding scalp of female pattern hair loss in Asian.

While many gene expression studies have focused on male pattern baldness (MPB), few studies have investigated the genetic differences between bald and non-bald hair follicles in female pattern hair loss (FPHL). This study aimed to identify molecular biomarkers associated with FPHL through genetic analysis of paired bald and non-bald hair follicles from 18 FPHL patients, using next-generation sequencing (NGS) techniques. RNA transcriptome analysis was performed to identify differentially expressed genes (DEGs) between bald and non-bald hair follicles in FPHL. The DEGs were validated using real-time PCR, and protein expression was confirmed through immunohistochemistry and western blot analysis. Our findings suggest that HOXB13, SFRP2, PTGDS, CXCR3, SFRP4, SOD3, and DCN are significantly upregulated in bald hair follicles compared to non-bald hair follicles in FPHL. SFRP2 and PTGDS were found to be consistently highly expressed in bald hair follicles in all 18 samples. Additionally, elevated protein levels of SFRP2 and PTGDS were confirmed through western blot and immunohistochemical analysis. Our study identified SFRP2 and PTGDS as potential biomarkers for FPHL and suggests that they may play a role in inducing hair loss in this condition. These findings provide a foundation for further research on the pathogenesis of FPHL and potential therapeutic targets.

The association between XPD rs13181 and rs1799793 polymorphism and oral cancer risk: evidence from a meta-analysis.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) are common in genes and can lead to dysregulation of gene expression in tissues, which can affect carcinogenesis. Many studies reporting the association between xeroderma pigmentosum group D (XPD) polymorphisms of rs13181 and rs1799793 with oral cancer risk, but with conflicting and inconclusive results. METHODS: We performed a comprehensive and systematic search through the PubMed, Elsevier, Web of science, and Embase databases, twelve studies were included in the meta-analysis to determine whether XPD rs13181 and rs1799793 polymorphism contributed to the risk of oral cancer. RESULTS: The pooled date indicated a significant association between the rs13181 polymorphism and oral cancer risk for the allele comparison model (odds ratio, OR = 1.60, 95% confidence intervals, CI = 1.09-2.35, P = 0.02), the dominant model (OR = 1.74, 95% CI = 1.08-2.82, P = 0.02), and the heterozygote model (OR = 1.59, 95% CI = 1.02-2.49, P = 0.04). For the XPD rs1799793 polymorphism, it is not associated with the incidence of oral cancer under any model. Subgroup analyses based on ethnicity indicated that the rs13181 polymorphism increased the risk of oral cancer among Asians according to the allele comparison model (OR = 1.97, 95% CI = 1.10-3.51, P = 0.02), the dominant model (OR = 2.35, 95% CI = 1.25-4.44, P = 0.008), the heterozygote model (OR = 2.05, 95% CI = 1.15-3.66, P = 0.01), and the homozygous model (OR = 2.47, 95% CI = 1.06-5.76, P = 0.04). CONCLUSION: Our meta-analysis suggests a positive correlation between XPD rs13181polymorphism and the development of oral cancer among Asians, but a negative correlation among Caucasians populations.

A multicenter, double-blind, randomized, parallel-group, active-controlled, phase 3 clinical trial to compare the effectiveness and safety of two botulinum toxin type A formulations for improving moderate to severe glabellar wrinkles in Asians.

Botulinum toxin type A (BoNT-A) was first isolated in 1946, and since then, several formulations have been developed and widely used to treat wrinkles by inducing muscle paralysis. This multicenter, double-blind, randomized, parallel-group, active-controlled phase 3 clinical trial was designed to evaluate the efficacy and safety of a newly developed BoNT-A formulation, BMI2006, in improving moderate to severe glabellar wrinkles and to compare with existing onabotulinumtoxin A (OBoNT) injections. A total of 276 subjects were enrolled and received 20 units of the randomized material, which was intramuscularly injected into five different locations on the forehead. The primary endpoint, assessed at 4 weeks, showed no statistically significant difference in the improvement rate of glabellar wrinkles between the two groups, with BMI2006 demonstrating non-inferiority to comparator BoNT-A. Secondary endpoints, evaluated by both treating investigators and independent investigators, also exhibited similar improvement rates throughout the study period. Both groups reported high levels of satisfaction with no statistical difference between the two groups. Safety evaluations indicated mild and transient adverse events, with no serious reactions observed. In conclusion, BMI2006 is an effective and safe BoNT-A for treating glabellar wrinkles with an expected duration of action between 8 and 12 weeks.

Comparison of the Detection Rate and Specificity of Irregular Red Blood Cell Antibodies Between First-Time Pregnant Women and Women With a History of Multiple Pregnancies Among 18,010 Chinese Women.

Background: There is insufficient evidence to assess the risk of the production of clinically important alloimmune irregular red blood cell (RBC) antibodies in first-time pregnant women. Methods: Using the microcolumn gel antiglobulin method, 18,010 Chinese women with a history of pregnancy and pregnant women were screened for irregular RBC antibodies, and for those with positive test results, antibody specificity was determined. The detection rate and specificity of irregular RBC antibodies in women with a history of multiple pregnancies (two or more) and first-time pregnant women were determined. Results: In addition to 25 patients who passively acquired anti-D antibodies via an intravenous anti-D immunoglobulin injection, irregular RBC antibodies were detected in 121 (0.67%) of the 18,010 women. Irregular RBC antibodies were detected in 93 (0.71%) of the 13,027 women with a history of multiple pregnancies, and antibody specificity was distributed mainly in the Rh, MNSs, Lewis, and Kidd blood group systems; irregular RBC antibodies were detected in 28 (0.56%) of the 4983 first-time pregnant women, and the antibody specificity was distributed mainly in the MNSs, Rh, and Lewis blood group systems. The difference in the percentage of patients with irregular RBC antibodies between the two groups was insignificant (χ 2 = 1.248, P > 0.05). Of the 121 women with irregular RBC antibodies, nine had anti-Mur antibodies, and one had anti-Dia antibodies; these antibodies are clinically important but easily missed because the antigenic profile of the reagent RBCs that are commonly used in antibody screens does not include the antigens that are recognized by these antibodies. Conclusion: Irregular RBC antibody detection is clinically important for both pregnant women with a history of multiple pregnancies and first-time pregnant women. Mur and Dia should be included in the antigenic profile of reagent RBCs that are used for performing antibody screens in the Chinese population.

The effect of second-person self-talk on performance and motivation in Japanese individuals.

Talking to oneself using the second-person pronoun ["you" has been shown to enhance performance and autonomous motivation in English speakers. However, there is a lack of evidence on whether it can be replicated for speakers of other languages, such as Japanese, in which the grammatical subject is usually omitted in daily conversation. Based on self-determination theory, the present study examined the effects of second-person self-talk for a sample of Japanese individuals on task performance, intrinsic motivation, and three styles of extrinsically motivated regulations: identified, introjected, and external. We randomly assigned 411 undergraduate students to either an experimental group (second-person self-talk, first-person self-talk, and non-subject self-talk) or a control group. An anagram task was used to assess performance. No significant difference was found between the four groups in intrinsic motivation or performance. For extrinsic regulations, the results showed that first-person self-talk led to higher external regulation than non-subject self-talk and the control group. The possible reason for contradictory findings with our hypothesis and implications have been discussed.

Genetic polymorphisms of BACH2, a key gene regulating Th2 immune response, increasing risk of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is an allergic disease characterized by the dominant differentiation of T helper cell 2 (Th2). BACH2 plays a key role in regulating Th2 immune response. This study aimed to explore the association between BACH2 single nucleotide polymorphism (SNPs) and susceptibility to AR. METHODS: Han population from northern Shaanxi, China was chosen as subjects. After the DNA extraction from the peripheral blood of subjects, genotyping was completed through the Agena MassARRAY platform. Logistic regression analysis was used to assess the association. Multivariate dimensionality reduction (MDR) was used to evaluate the effect of the interaction between 'SNP-SNP' on susceptibility to AR. Using false-positive report probability (FPRP) analysis to test whether the significant results obtained in this study were noteworthy. RESULTS: BACH2-rs905670 and -rs2134814 were significantly associated with increased risk of AR. The mutant allele 'A' of rs905670 (OR = 1.36, p = 0.018) and mutant allele 'G' of rs2134814 (OR = 1.34, p = 0.027) were risk genetic factors for AR. The above genetic association was further observed in the stratified analysis: BACH2-rs905670 and-rs2134814 were significantly associated with an increased risk of AR in females, aging older than 43 years, and participants working and living in the loess hills (OR > 1, p < 0.05). CONCLUSION: BACH2-rs905670 and -rs2134814 are significantly associated with increasing AR risk.

Comprehensive genetic analysis uncovers the mutational spectrum of MFRP and its genotype-phenotype correlation in a large cohort of Chinese microphthalmia patients.

PURPOSE: Microphthalmia is a severe congenital ocular disease featured by abnormal ocular development. The aim of this study was to detail the genetic and clinical characteristics of a large cohort of Chinese patients with microphthalmia related to MFRP variants, focusing on uncovering genotype-phenotype correlations. METHODS: Fifty microphthalmia patients from 44 unrelated Chinese families were recruited. Whole-exome sequencing (WES) was conducted to analyze the coding regions and adjacent intronic regions of MFRP. Axial lengths (AL) were measured for all probands and available family members. Protein structures of mutations with high frequency in our cohort were predicted. The genotype-phenotype correlations were explored by statistical analysis. RESULTS: Sixteen MFRP variants were detected in 17 families, accounting for 38.64 % of all microphthalmia families. There were 9 novel mutations (c.427+1G>C, c.428-2A>C, c.561_575del:p.A188_E192del, c.836G>A:p.C279Y, c.1010_1021del:p.H337_E340del:p.Y479*, c.1516_1517del:p.S506Pfs*66, c.1561T>G:p.C521G, c.1616G>A:p.R539H, and c.1735C>T:p.P579S) and six previously reported variants in MFRP, with p.E496K and p.H337_E340del being highly frequent, found in eight (47.06 %) and two families (11.76 %), respectively. Seven variants (43.75 %) were located in the C-terminal cysteine-rich frizzled-related domain (CRD) (7/16, 43.75 %). Protein prediction implicated p.E496K and p.H337_E340del mutations might lead to a destabilization of the MFRP protein. The average AL of all 42 eyes was 16.02 ± 1.05 mm, and 78.36 % of eyes with AL < 16 mm harbored p.E496K variant. Twenty-six eyes with variant variant had shorter AL than that of the other 16 eyes without this variant (p = 0.006), highlighting a novel genotype-phenotype correlation. CONCLUSIONS: In this largest cohort of Chinese patients with microphthalmia, the 9 novel variants, high frequency of p.E496W, and mutation hotspots in CRD reveals unique insights into the MFRP mutation spectrum among Chinese patients, indicating ethnic variability. A new genotype-phenotype correlation that p.E496K variant associated with a shorter AL is unveiled. Our findings enhance the current knowledge of MFRP-associated microphthalmia and provide valuable information for prenatal diagnosis as well as future therapy.

Comparison of whole-blood sirolimus concentrations measured by EMIT-based Siemens Viva-ProE® System and LC-MS/MS in Chinese transplant patients.

Sirolimus (SRL) is commonly used in transplant patients to prevent organ transplant rejection. The current guidelines recommend to perform SRL therapeutic drug monitoring regularly to improve treatment outcomes and avoid adverse effects. Consequently, a precise and accurate method for determining SRL is crucial in clinical practice. Currently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassays have been widely adopted for determining SRL concentrations. However, previous studies have shown that immunoassays exhibit a positive bias compared to LC-MS/MS. As the new updated version of the EMIT-based Viva-E® System (SVPS), this study aims to compare SRL blood concentrations measured by the SVPS and LC-MS/MS. The residual whole-blood samples obtained from transplant patients were simultaneously analyzed using the SVPS and LC-MS/MS, respectively. The correlation between the two assays was analyzed using the linear regression analysis and Deming linear regression. The Pearson correlation coefficient and Intraclass correlation coefficient (ICC) analysis were executed. The Paired Wilcoxon test and Bland-Altman analysis were performed to assess the concordance between the two methods. The SVPS considerably increased SRL concentration value by 46.62 % as compared to the LC-MS/MS method. When SRL concentrations measured by the SVPS were above 4.0 ng/mL, there was no significant difference between the corrected SVPS concentrations after using the Deming linear regression equation, indicating their interchangeability. Given the significant disparities observed between EMIT and LC-MS/MS, it is crucial to indicate the methodology and instruments in both TDM reports and future clinical guidelines. Our study also provides the conversion formulas between the SVPS and LC-MS/MS, which can be applied as a reference for different clinical centers.